Prediction of protein mutational free energy: benchmark and sampling improvements increase classification accuracy

SEATTLE, WA March 20, 2020 — Software to predict the change in protein stability upon point mutation is a valuable tool for a number of biotechnological and scientific problems. To facilitate the development of such software and provide easy access to the available experimental data, the ProTherm database was created. Biases in the methods and types of information collected has led to disparity in the types of mutations for which experimental data is available. For example, mutations to alanine are hugely overrepresented whereas those involving charged residues, especially from one charged residue to another, are underrepresented. ProTherm subsets created as benchmark sets that do not account for this often underrepresented certain mutational types. This issue introduces systematic biases into previously published protocols’ ability to accurately predict the change in folding energy on these classes of mutations. To resolve this issue, we have generated a new benchmark set with these problems corrected. We have then used the benchmark set to test a number of improvements to the point mutation energetics tools in the Rosetta software suite.


Brandon Frenz, Steven Lewis, Indigo King, Hahnbeom Park, Frank DiMaio, Yifan Song

About Cyrus Biotechnology

Cyrus Biotechnology, Inc. is a privately-held Seattle-based biotechnology software company offering software and partnerships for protein engineering to accelerate discovery of biologics and small molecules for the Biotechnology, Pharmaceutical, Chemical, Consumer Products and Synthetic Biology industries. Cyrus methods are based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington and HHMI, the most powerful protein engineering software available. Cyrus customers include 13 of the top 20 Global Pharmaceutical firms and is financed by leading investors in both Technology and Biotechnology, including Trinity Ventures, Orbimed, Springrock Ventures, Alexandria Venture Investments, and W Fund.

Cyrus Biotechnology, Inc.
Lucas Nivon, 206-258-6561